Myeloproliferative diseases are diseases in which hematopoietic stem cells exhibit an impairment in their differentiation capacity and/or an impairment of their dependence on a specific growth factor.
Blood cells derive from a small number of stem cells capable of self-nenewal which generate progenitor cells irreversibly committed to the production of one or a few hematopoietic lines. Precise control of each step of differentiation is necessary in order to ensure a stable level of the different specialized cells as well as to provide a precise response to stimulations caused by stress. The controls are usually due to the effect of interactions between cells, either resulting from contact with the hematopoietic micro-environment or from the release of specific cytokines. The breakdown of the control systems leads either to cytopenias or to an uncontrolled cellular proliferation which may affect one or more lines depending on the nature of the lesion. The proliferation of several hematopoietic lines may lead to a myeloproliferative disease. Such diseases can be induced by retroviruses carrying oncogenes such as the retrovirus MPLV, an abbreviation for "myeloproliferative leukemia virus" which is a retrovirus defective with respect to its replication.
It is known that the murine retrovirus MPLV causes a severe hematological disorder in adult mice of most strains, characterized by a dramatic proliferation and a differentiation of several hematopoietic lines. The most acute aspect of this disease is the suppression of the in vitro dependence on growth factors for most of the hematopoietic progenitor cells. The natural MPLV isolate has been described as being a complex of two viral entities: a murine virus F-MuLV (Friend replication competent ecotropic murine leukemia virus) and a virus defective with respect to its replication now designated by the term MPLV. The pseudotyping of the defective particles with other ecotropic or amphotropic MuLV viruses enables the initial disease to be reproduced. It has been shown that the proviral DNA of MPLV and the DNA of F-MuLV are structurally similar except in the envelope region.
The inventors have now identified a sequence of cellular origin transduced in the rearranged gene of the MPLV envelope and which proves to be conserved in the mammalian genome.
The identification of this sequence has enabled its importance in phenomena which have similarities with a myeloproliferative disease to be demonstrated.
The invention thus relates to a polypeptide capable of playing a role when it is produced by a virus of the MPLV type in the disturbances caused during myeloproliferative diseases. The invention also relates to nucleotide sequences coding for this polypeptide.
The inventors have made the very interesting observation that the protein sequence of the polypeptide of the invention exhibits pronounced analogies with certain amino acid sequences of growth factor receptors. Consequently, the invention makes possible the identification of the mechanisms of the disease linked to the infection by the retrovirus MPLV and suggests agents for the detection of a disease of the same type in man and optionally, for its treatment.